PROJECT SUMMARY Title: Ecology of African Highland Malaria In the past decade, massive scale-up of insecticide-treated nets (ITN) and indoor residual spraying (IRS), together with the introduction of artemisinin-combination treatments, have led to substantial reductions in malaria prevalence and incidence in African highlands. However, rising insecticide resistance and increased outdoor transmission have greatly hampered the effectiveness of ITN and IRS because the current indoor-based interventions do not target the outdoor-biting mosquitoes. Consequently, most highland sites maintain sustained low- level transmission while some others have recently experienced resurgence in malaria rates. Therefore, new supplemental interventions that can tackle outdoor transmission and pyrethroid insecticide resistance are urgently needed. The central objective of this competing renewal application is to determine the efficacy and cost-effectiveness of EPA-approved long-lasting microbial larvicides in reducing malaria transmission and clinical malaria incidence in western Kenya highlands. The three specific aims are: 1) to examine mechanisms regulating larval habitat productivity, 2) to determine the efficacy of long-lasting microbial larvicides on the reduction of malaria transmission and clinical malaria incidence using a cluster randomized study, and 3) to determine the cost-effectiveness of the long-lasting microbial larviciding program as compared to other malaria control interventions and evaluate its impact on non-target organisms. Through comprehensive evaluation of potentially cost-effective long-lasting microbial larvicides, this project will provide critically needed data on whether long-lasting microbial larvicides can be scaled up as a supplemental malaria control tool to further reduce malaria incidence in African highlands. Malaria outdoor transmission control is presently a highly significant and urgent issue in malaria control across Africa, and thus, our results will have broad implications on malaria prevention and control in endemic and epidemic regions of Africa.